Coronary artery disease (CAD) remains the leading cause of death in the United States. Due to the substantial morbidity and mortality related to CAD, stress single photon emission CT (SPECT) myocardial perfusion imaging has emerged as an important noninvasive means of evaluating patients with suspected and known CAD. The preferred stress modality is exercise. However, many patients require pharmacologic stress with vasodilators or β-agonists due to the inability to perform adequate exercise. Compared to exercise stress, pharmacologic stress is associated with more adverse effects, poorer nuclear image quality, and higher cardiac event rates. Protocols which combine pharmacologic stress with exercise improve the side effect profile of pharmacologic stress, improve image quality, and provide the clinician with objective data on functional capacity and prognosis.